Historically, the most widely accepted classification scheme for acute leukemias has been based on morphological and cytochemical features. This method for classification was proposed by the French-American-British (FAB) group..sup.1,2 The FAB classification scheme, shown in Table 1, is the primary method used for classification of acute leukemias by visual, microscopic analysis. Accordingly, it remains dependent upon the cell preparation, method of chemical staining and subjectivity of the technician "reading" the slide. More recently, immunophenotyping by flow cytometry has been investigated for assisting in characterizing and subclassifying acute leukemias as B-lymphoid, T-lymphoid, myeloid or undifferentiated..sup.3,4,5
In normal bone marrow, unique identification of cell lineage and discrimination between stages of maturation within each cell lineage are possible using flow cytometry..sup.6,7,8,9,10,11,12 In leukemias, however, cell-surface antigen expression often does not follow the normal maturation pathways, resulting in asynchronous or aberrant expression of cell-surface antigens..sup.7,13,14,15,16
TABLE I ______________________________________ Acute Myeloblastic Leukemia Acute Lymphoblastic (AML) Leukemia (ALL) ______________________________________ M0 undifferentiated L1 Lymphoblasts, myeloblastic leukemia small scanty cytoplasm M1 Myeloblastic without L2 Heterogeneous, differentiation large blast with variable cytoplasm M2 Myeloblastic with L3 Heterogeneous, differentiation large blast with vacuolated cytoplasm M2baso Myeloblastic with basophilia M3 Hypergranular promyelocytic M3v Microgranular promyelocytic M4 Myelomonocytic M4eo Myelomonocytic with eosinophilia M5 Monocytic (M5a-Monocytic without differentiation) (M5b-Monocytic with differentiation) M6 Erythroleukemia M7 Megakaryoblastic ______________________________________
The aberrant expression of antigens in leukemias complicates the process of characterizing and assigning a lineage to the leukemic cell population.
With respect to the acute leukemias listed in Table I, for example, B-lineage-associated antigens are relatively more specific than the T-lymphoid and myeloid associated antigens, however, T-lymphoid associated antigens have been described on both myeloid and B-lymphoid leukemias..sup.13,14,15,16 In contrast, no lineage-specific antigens have been characterized for the acute myeloid leukemias..sup.18,19 As a result, assignment of leukemic samples to T-lymphoid, myeloid or undifferentiated categories is more difficult, due to the need for more extensive interpretation of the data obtained from both the antigenic and light scatter profiles.
Assigning a lineage to a leukemic cell population is important because different leukemias are treated with different therapies. Accordingly, it is an object of this invention to provide a single, reliable and objective method for classifying leukemias. Once classified, the method further may be used to monitor progression and/or treatment of the disease.